Synthesis and assembly of brain myelin will be studied in rats 18 days of age (a time when the rate of accumulation of myelin is high). Following injection of the appropriate radioactive precursor, and sacrifice of rats at early (30 min to 24 hr) time intervals, we will determine specific activity of individual myelin specific lipids or proteins in their relevant subcellular fractions. Using these experiments as a guide, sensitive double-label protocols will be used to establish precursor relationships in the transfer of myelin specific components (basic protein, proteolipid protein, cerebroside, sulfatide, etc.) from one subcellular fraction to another. In particular the hypothesis that myelin subfractions have physiological significance will be tested (is there an addition of specific components in a particular order which causes a decrease in buoyant density during the assembly and maturation process?). Long-term experiments will be carried out to determine turnover rates of myelin lipids ad proteins. A double isotope methodology will be used to attempt to clarify discrepancies in the literature regarding the half-life of myelin components labeled with different precursors. Metabolism of lipids and myelin proteins of rat brain myelin will be studied in normal animals and in animals perturbed with respect to assembly or maintenance of the myelin sheath by: starvation, treatment with heavy metals, treatment with cholesterol inhibitors, hyperphenylalaninemia, experimental allergic encephalomyelitis, and genetic lesion (Quaking mouse). Sensitive double-label techniques will be used to compare synthesis of myelin proteins and lipids in experimental animals and controls. Long-term double-label experiments will be conducted to compare relative turnover rates of myelin lipids and proteins in experimental animals and controls.